Drugs such as amoxicillin, ampicillin, penicillin V and erythromycin are antibacterial drugs which are available for oral dispensation in a gelatin capsule containing a specified dosage amount of the drug. For patients who have difficulty swallowing capsules, e.g., the very young and the very old, the drugs can be suspended in an aqueous solution, such as a sugar type syrup. However, the aforementioned drugs are quite unstable in water, even when stored at temperatures of about 4.degree. C., and very unstable at room temperature. Thus the drug solutions or suspensions have a very short shelf life, even at low temperatures. Further, they have an unpleasant taste which makes them unpalatable.
Beta-lactam antibiotics are orally inactive, and must be combined with an enhancer to promote their absorption into the body of the patient. Such enhancers are known, for example see U.S. Pat. No. 4,525,339, and include aliphatic fatty acids or acid glycerides. The fatty acids are generally C.sub.2 to C.sub.18 fatty acids, which can be straight or branched chain, saturated or unsaturated, their mono-, di- or triglycerides or mixtures thereof, and can also be partial or total esters of propylene glycol, polyethylene glycol and carbohydrates of C.sub.2 to C.sub.12 fatty acids and pharmaceutically acceptable esters and ethers of said glyceride. Encapsulating the drug in the enhancer is known also.
It would be quite advantageous to be able to formulate the above-described drugs, in a liquid-deliverable form, which would, nevertheless, be stable over the course of long term storage, i.e., for up to about 18 months, even at room temperature. To achieve this elusive objective without compromising the efficacy of the drugs, the drugs would have somehow to be isolated from the water in the storage/delivery medium, yet be released at the appropriate time and in the desired systemic environment of a recipient's body. In satisfying these objectives, drugs could be coated uniformly and completely with a water-impervious coating. In order for the encapsulated drug particles to stay suspended in an aqueous solution or emulsion for administration in liquid form, the individual particle size of the encapsulated drug particles would have to be very small, on the order of 1500 micrometers or less; otherwise the drug particles would settle out of the solution or suspension, and the dosage would be inaccurate.
Therefore, a suitable coating or encapsulant material must be impervious to water (to withstand long-term storage), but for efficacious patient treatment must dissolve in the stomach or other appropriate portion of the digestive tract, depending on the drug to be administered and the dosage required. Coatings having particular solubility characteristics can be used to provide controlled or delayed release of the drug in the patient.
Unfortunately, no one encapsulant coating is known to date that is effective to carry out all of the above-described objectives. Thus there is a need to be able to apply more than one encapsulant material, successively and uniformly, over very small particle size granules of the drug to be administered. Thus, it would be highly desirable to provide a practicable method for preparing small microspheres, on the order of about 500 micrometers, at the center of each of which lie individual drug particles. Each drug particle is encapsulated by successive encapsulants, each of a material which dissolves in a particular systemic environment in order to expose the next, more interior encapsulant layer for subsequent reaction at a distinctly new systemic environment, and ultimately for exposing the drug particle at the appropriate time and systemic loci.